title: Supraphysiologic extracellular pressure inhibits intestinal epithelial wound healing independently of luminal nutrient flow.
abstract: BACKGROUND
  Luminal pressure may injure the gut mucosa in obstruction, ileus, or inflammatory bowel disease.
  
  
  METHODS
  We formed Roux-en-Y anastomoses in 19 mice, creating proximal and defunctionalized partially obstructed limbs and a distal limb to vary luminal pressure and flow. We induced mucosal ulcers by serosal acetic acid, and assessed proliferation (proliferating cell nuclear antigen) and ERK (immunoblotting). Parallel studies compared Caco-2 enterocyte migration and proliferation after pressure and/or ERK blockade.
  
  
  RESULTS
  At 3 days, anastomoses were probe-patent, proximal and distal limbs contained chyme, and defunctionalized limbs were empty. The proximal and defunctionalized limbs showed increased pressure and slower healing despite increased proliferation, ERK protein, and ERK activation. In vitro, pressure decreased Caco-2 migration across collagen or fibronectin, stimulated proliferation, and activated ERK. However, ERK blockade did not prevent pressure effects.
  
  
  CONCLUSIONS
  Luminal pressure during obstruction or ileus may impair mucosal healing independently of luminal flow despite increased mitosis and ERK activation.
authors.affiliation: Departments of Surgery, Anatomy and Cell Biology, John D. Dingell VA Medical Center and Wayne State University, Surgical Service (11S), 4646 John R. St., Detroit, MI 48201, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Flanigan
authors.forename: Cheri R
authors.initials: CR
authors.lastname: Owen
authors.forename: Christopher
authors.initials: C
authors.lastname: Gayer
authors.forename: Marc D
authors.initials: MD
authors.lastname: Basson
mesh_terms: D019342:Acetic Acid; D000713:Anastomosis, Roux-en-Y; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D048053:Mitogen-Activated Protein Kinase 6 / Q000096:biosynthesis*; D008938:Mitosis / Q000502:physiology; D011312:Pressure; D014945:Wound Healing / Q000502:physiology*
chemical_list: D005419:Flavonoids; C474633:Mapk6 protein, mouse; D048053:Mitogen-Activated Protein Kinase 6; D019342:Acetic Acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D004121:Dimethyl Sulfoxide